Body surface area-based versus concentration-based intraperitoneal perioperative chemotherapy in a rat model of colorectal peritoneal surface malignancy: pharmacologic guidance towards standardization

// Lieselotte Lemoine 1, 2 , Elsy Thijssen 3 , Robert Carleer 3 , Jirka Cops 1, 4 , Veerle Lemmens 5 , Peter Van Eyken 6 , Paul Sugarbaker 7 and Kurt Van der Speeten 1, 2 1 Department of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium 2 Department of Surgical Oncology, Ziekenhuis Oost-Limburg, Genk, Belgium 3 Department of Applied and Analytical Chemistry, Institute for Materials Research (IMO), Hasselt University, Diepenbeek, Belgium 4 Department of Medicine and Life Sciences, Biomedical Research Institute, Rehabilitation Research Center, Hasselt University, Hasselt, Belgium 5 Department of Medicine and Life Sciences, Dynamic Bioimaging Laboratory, Advanced Optical Microscopy Centre, Biomedical Research Institute (BIOMED), Hasselt University, Hasselt, Belgium 6 Department of Pathology, Ziekenhuis Oost-Limburg, Genk, Belgium 7 Center for Gastrointestinal Malignancies, MedStar Washington Hospital Center, Washington, DC, USA Correspondence to: Lieselotte Lemoine, email: lieselotte.lemoine@uhasselt.be Keywords: peritoneal surface malignancy; colorectal cancer; HIPEC; oxaliplatin; dosimetry Received: November 24, 2018 Accepted: January 28, 2019 Published: February 15, 2019 ABSTRACT Worldwide, cytoreductive surgery (CRS) and hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) are used in current clinical practice for colorectal peritoneal surface malignancy (PSM) treatment. Although, there is an acknowledged standardization regarding the CRS, we are still lacking a much-needed standardization amongst the various intraperitoneal (IP) chemotherapy protocols, including the HIPEC dosing regimen. We should rely on pharmacologic evidence building towards such a standardization. The current IP chemotherapy dosing regimens can be divided into body surface area (BSA)-based and concentration-based protocols. A preclinical animal study was designed to evaluate pharmacologic advantage (PA), efficacy and survival. WAG/Rij rats were IP injected with the rat colonic carcinoma cell line CC-531. Animals were randomized into three groups: CRS alone or CRS combined with oxaliplatin-based HIPEC (either BSA- or concentration-based). There was no difference in PA between the two groups (p=0.283). Platinum concentration in the tumor nodule was significantly higher in the concentration-based group ( p <0.001). Median survival did not differ between the treatment groups ( p <0.250). This preclinical study, in contrast to previous thinking, clearly demonstrates that the PA does not provide any information about the true efficacy of the drug and emphasizes the importance of the tumor nodule as pharmacologic endpoint.